Silibins (silybins) are well known flavonolignans from milk thistle (Silybum marianum L.) having valuable biological activities such as hepatoprotective and effects against liver disorders, as well as anti-inflammatory, antifibrotic, immunomodulating, and anticancer activities. Due to their low water solubility, they have low bioavailability.
In this study, the molecular encapsulation of the main isomer silibinin A and its saturated fatty acid (from caprylic to behenic acid) bioconjugates by natural α-, β- and γ-cyclodextrin (α-, β-, and γ-CD) have been theoretically investigated. The most stable conformers of silibinin were docked in CDs using various starting orientations. Molecular mechanics method (MM+) from HyperChem molecular modeling package, with a Polak-Ribiere optimization algorithm were applied. Better interactions were obtained for long-chain silibinin-fatty acid bioconjugates with β- and γ-CD (15.6-25.2 and 25.6-36.8 kcal/mol, respectively) in comparison with α-CD (11.3-22.7 kcal/mol). Furthermore, the hydrophobicity of bioconjugates well correlates with the guest-host interaction energy, suggesting the possibility to enhance the bioavailability by two mechanisms: increasing the hydrophobicity of silibinin by bioconjugation, followed by CD nanoencapsulation for better water solubility.